Stereospecific synthesis of a few 3,4-disubstitued beta-lactams derived from polyaromatic ferrocenyl imines is achieved following Staudinger cycloaddition reaction. The exclusive formation of trans-beta-lactams is observed. The stereochemistry of these resulting beta-lactams formation reaction is unprecedented.

The number of circulating tumor cells (CTCs) found in blood is known to be a prognostic marker for recurrence of primary tumors, however, most current methods for isolating CTCs rely on cell surface markers that are not universally expressed by CTCs. Dielectrophoresis (DEP) can discriminate and manipulate cancer cells in microfluidic systems and has been proposed as a molecular marker-independent approach for isolating CTCs from blood. To investigate the potential applicability of DEP to different cancer types, the dielectric and density properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic field-flow fractionation (DEP-FFF) and compared with like properties of the subpopulations of normal peripheral blood cells. We show that all of the NCI-60 cell types, regardless of tissue of origin, exhibit dielectric properties that facilitate their isolation from blood by DEP. Cell types derived from solid tumors that grew in adherent cultures exhibited dielectric properties that were strikingly different from those of peripheral blood cell subpopulations while leukemia-derived lines that grew in non-adherent cultures exhibited dielectric properties that were closer to those of peripheral blood cell types. Our results suggest that DEP methods have wide applicability for the surface-marker independent isolation of viable CTCs from blood as well as for the concentration of leukemia cells from blood.

Although dielectrophoresis (DEP) has great potential for addressing clinical cell isolation problems based on cell dielectric differences, a biological basis for predicting the DEP behavior of cells has been lacking. Here, the dielectric properties of the NCI‐60 panel of tumor cell types have been measured by dielectrophoretic (DEP) field‐flow fractionation, correlated with the exterior morphologies of the cells during growth, and compared with the dielectric and morphological characteristics of the subpopulations of peripheral blood. In agreement with earlier findings, cell total capacitance varied with both cell size and plasma membrane folding and the dielectric properties of the NCI‐60 cell types in suspension reflected the plasma membrane area and volume of the cells at their growth sites. Therefore, the behavior of cells in DEP‐based manipulations is largely determined by their exterior morphological characteristics prior to release into suspension. As a consequence, DEP is able to discriminate between cells of similar size having different morphological origins, offering a significant advantage over size‐based filtering for isolating circulating tumor cells, for example. The findings provide a framework for anticipating cell dielectric behavior on the basis of structure–function relationships and suggest that DEP should be widely applicable as a surface marker‐independent method for sorting cells.

Microwave-induced stereospecific synthesis of beta-Lactams derived from polyaromatic imines has been realized.

This study describes the symmetric synthesis of novel β-lactams derived from chrysene directed towards their SAR, as well as their biological activities against several cancer cell lines in vitro. To our knowledge, this is the first report on the synthesis and biological evaluation of optically active anticancer β-lactams. That these anticancer effects are not uniform against all tumor lines suggests that the target of the action of these compounds is highly specific.

We describe herein asymmetric synthesis of a novel anticancer β-lactam following Staudinger reaction with chiral carbohydrate as the ketene component with an achiral imine. The in vitro cytotoxicity studies of these β-lactams are also reported here.

We describe herein the synthesis of novel 6,12-distributed chrysene as potent anticancer agents. In vitro and in vivo studies are also reported here.

The novel synthesis of dibenzofluorene has been achieved by a cyclodehydration method. Several derivatives have also been prepared using this hydrocarbon. These compounds have been tested against a number of cancer cell lines in vitro, and useful selectivity has been observed.

Currently available anticancer drugs are cytotoxic to normal as well as to neoplastic cells, therefore the synthesis of β-lactams as new and novel anticancer agents is extremely significant. We previously developed synthetic methods for the preparation of β-lactams and anticancer agents resulting from polyaromatic amines. There have also been reports on the synthesis and biological evaluation of novel racemic β-lactams as anticancer agents. In cell cycle analysis, these compounds demonstrated a G2 blockage against sensitive tumor cell lines. In the present study, useful and selective biological activities of chrysene β-lactams are described.

Stereocontrolled synthesis of racemic and chiral novel beta-lactams using polyaromatic imines has been accomplished. Domestic and automated microwave-induced reactions have been investigated for the preparation of these types of beta-lactams. A preliminary mechanism of this reaction has been advanced. Formation of trans-beta-lactams has been explained through isomerization of the enolates formed during the reaction of acid chloride with imines in the presence of tertiary base. A donor-acceptor complex pathway has been believed to be involved in the formation of cis-beta-lactams. The effect of a peri hydrogen has been found to be significant in controlling the stereochemistry of the beta-lactams. Structure-activity relationship has identified beta-lactams with anticancer activity. The presence of an acetoxy group has proven very important for anticancer activity. The preparation and mechanism of action of several other new anticancer beta-lactams have also been explored.

The scale-invariant property of the cytoplasmic membrane of biological cells is examined by applying the Minkowski-Bouligand method to digitized scanning electron microscopy images of the cell surface. The membrane is found to exhibit fractal behavior, and the derived fractal dimension gives a good description of its morphological complexity. Furthermore, we found that this fractal dimension correlates well with the specific membrane dielectric capacitance derived from the electrorotation measurements. Based on these findings, we propose a new fractal single-shell model to describe the dielectrics of mammalian cells, and compare it with the conventional single-shell model (SSM). We found that while both models fit with experimental data well, the new model is able to eliminate the discrepancy between the measured dielectric property of cells and that predicted by the SSM.

The application of dielectrophoretic field-flow fractionation (depFFF) to the isolation of circulating tumor cells (CTCs) from clinical blood specimens was studied using simulated cell mixtures of three different cultured tumor cell types with peripheral blood. The depFFF method can not only exploit intrinsic tumor cell properties so that labeling is unnecessary but can also deliver unmodified, viable tumor cells for culture and/or all types of molecular analysis. We investigated tumor cell recovery efficiency as a function of cell loading for a 25 mm wide x 300 mm long depFFF chamber. More than 90% of tumor cells were recovered for small samples but a larger chamber will be required if similarly high recovery efficiencies are to be realized for 10 mL blood specimens used CTC analysis in clinics. We show that the factor limiting isolation efficiency is cell-cell dielectric interactions and that isolation protocols should be completed within approximately 15 min in order to avoid changes in cell dielectric properties associated with ion leakage.

As an approach to isolating tumor cells from fine needle biopsy specimens, we investigated a dielectric cell preparation method using an in vivo xenographic tumor model. Cultured human MDA-MB-435 tumor cells were grown as solid tumors in nude mice and fine needle aspiration biopsies were conducted. Biopsied cells were suspended in sucrose medium and collected on slides patterned with microelectrode arrays (electrosmears) energized by electrical signals in the range 10 to 960 kHz. The unlabeled cells adhered to characteristic regions of the slides in accordance with their morphology as a result of dielectric forces. Tumor cells were trapped between 40 and 60 kHz and were separated according to whether they were mitotic, large and complex, or small. Damaged tumor cells were captured at between 60 and 120 kHz; granulocytes between 70 and 90 kHz; lymphocytes between 85 and 105 kHz; healthy erythrocytes between 140 and 180 kHz, and damaged erythrocytes above 180 kHz. Using intrinsic cell characteristics, the electrosmear presented cell subpopulations from fine needle aspiration biopsy specimens in a manner that is compatible with automated slide-based analysis systems. The approach has the potential to facilitate the analysis of the role of cell subpopulations in disease.

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